NUCLEAR ANTIGENS WITH EPITOPIC HOMOLOGY TO THE CELL-SURFACE ANTIGENS - THE NEGLECTED DETERMINANTS OF MALIGNANT TRANSFORMATION

Nonhistone chromatin proteins with epitopes recognized by monoclonal a ntibodies (MAbs) directed against cancer cell surface antigens represe nt a highly unique group of nuclear antigens. Some of these nuclear an tigens constitute chromatin receptors for growth factors, which bind b oth growth factors and internalized MAbs directed against cell surface receptors. Analysis of the Nerve Growth Factor (NGF) receptors sugges ts that the cell surface receptors mediate activatory effect of NGF on cell growth, while chromatin receptors mediate inhibitory action of N GF on synthesis of rRNA. High expression of the cell surface receptors for NGF, or too low expression of the nuclear receptor, may contribut e to malignant transformation. Nicotine, which inhibits lysosomal degr adation of proteins, promotes nuclear accumulation of growth factors. Nicotine-stimulated chromatin binding of PDGFAA was found to activate RNA synthesis, which may explain the mechanism of nicotine-growth fact or co-carcinogenesis. Majority of antigenic epitopes localized in two cellular compartments, (cell surface and chromatin), do not belong to growth factor receptors and may represent targets for therapeutic MAbs .